For over a decade, animal research has demonstrated the ability of both agonists and antagonists to modulate alcohol consumption. More recently, two human trials have suggested that naltrexone is effective in decreasing relapse in recently abstinent alcoholics during ongoing rehabilitation services. The primary objectives of the proposed clinical pharmacology laboratory trial are: to determine a dose-effect function of naltrexone on subjective, physiological, neuroendocrine and psychomotor measures of acute alcohol intoxication; to determine the time course of effects and examine specific effects on the ascending vs. descending BAL limbs; to examine effects of naltrexone on alcohol pharmacodynamics; and to provide information on potential mechanisms for naltrexone effects in decreasing alcohol consumption in recently abstinent alcohol-dependent patients. Subjects were community-recruited, heavy drinking subjects, with no current medical or psychiatric problems. All subjects were admitted to the GCRC for three, 8-day experimental periods separated by a one week washout period to allow for randomization of chronic naltrexone dosing without carryover effects. Each subject received each naltrexone maintenance dose (0, 50 and 100 mg) once in random order over the course of the three experimental periods. Beginning on the day of admission and for the duration of each experimental period, subjects were maintained on a single dose of naltrexone with once daily dosing. Once steady state naltrexone levels had been achieved by day 4, subjects participated in three alcohol challenge sessions (0.0, 0.6 and 1.0 mg/kg) in random order on days 4, 6 and 8 of the experimental period. Physiologic, subjective and psychomotor performance effects were assessesd during each experimental session. We have recently completed subject recruitment and participation in the experimental sessions, and are currently analyzing study data. Preliminary findings suggest few differences in subjective or physiological responses following alcohol challenges across the naltrexone doses. A competitive renewal application will be submitted in April, 1997.